GM1 induces p38 and microtubule dependent ramification of rat primary microglia in vitro.
Microglia are immunologically competent cells in the central nervous system and considered to be a key player in brain inflammation. The morphological change of microglia has been shown to be linked to functional phenotypes both in vivo and in vitro. As an attempt to identify factors that regulate microglial morphology, we investigated the effect of gangliosides on microglial ramification in vitro. Brain gangliosides mixture and GM1 induced typical ramification of cultured rat primary microglia, however, GD1a and GT1b did not. Although GM1 significantly induced the expression of neurotrophin-3 (NT-3), NT-3 did not induce typical morphological changes in cultured rat primary microglia. SB203580 (an inhibitor of p38), and paclitaxel and nocodazole (microtubule-disrupting drugs) inhibited GM1-induced microglial ramification, but Jaki (an inhibitor of JAK), PD98059 (an inhibitor of Erk1/2), SP600125 (an inhibitor of JNK), and cytochalasin B and latrunculin B (actin polymerization inhibitors) did not, suggesting that GM1 induced ramification of microglia in p38- and microtubule-dependent manner. This in vitro system would be helpful in understanding the mechanisms of microglial ramification and physiological roles of gangliosides in microglia.
Park
Ji-Young
JY
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 442-721, Republic of Korea.
Kim
Hee Young
HY
Jou
Ilo
I
Park
Sang Myun
SM
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050257:Tubulin Modulators / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005732:Gangliosides; D007093:Imidazoles; D008070:Lipopolysaccharides; D020933:Neurotrophin 3; D011725:Pyridines; D050257:Tubulin Modulators; C021298:ganglioside, GD1a; D005677:G(M1) Ganglioside; C016481:trisialoganglioside GT1; D007371:Interferon-gamma; D020932:Nerve Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D017239:Paclitaxel; D015739:Nocodazole